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@article{1838631, author = {Krafčík, Daniel and Ištvánková, Eva and Džatko, Šimon and Víšková, Pavlína and FoldynovaandTrantirkova, S. and Trantírek, Lukáš}, article_location = {Basel}, article_number = {11}, doi = {http://dx.doi.org/10.3390/ijms22116042}, keywords = {in-cell NMR; G-quadruplex; ligand; drug; Bcl2; telomeric DNA; KRAS; BRACO19; PhenDC3; NMM}, language = {eng}, issn = {1422-0067}, journal = {International Journal of Molecular Sciences}, title = {Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy}, url = {https://www.mdpi.com/1422-0067/22/11/6042}, volume = {22}, year = {2021} }
TY - JOUR ID - 1838631 AU - Krafčík, Daniel - Ištvánková, Eva - Džatko, Šimon - Víšková, Pavlína - Foldynova-Trantirkova, S. - Trantírek, Lukáš PY - 2021 TI - Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy JF - International Journal of Molecular Sciences VL - 22 IS - 11 SP - 6042 EP - 6042 PB - Multidisciplinary Digital Publishing Institute SN - 14220067 KW - in-cell NMR KW - G-quadruplex KW - ligand KW - drug KW - Bcl2 KW - telomeric DNA KW - KRAS KW - BRACO19 KW - PhenDC3 KW - NMM UR - https://www.mdpi.com/1422-0067/22/11/6042 N2 - Recently, the H-1-detected in-cell NMR spectroscopy has emerged as a unique tool allowing the characterization of interactions between nucleic acid-based targets and drug-like molecules in living human cells. Here, we assess the application potential of H-1 and F-19-detected in-cell NMR spectroscopy to profile drugs/ligands targeting DNA G-quadruplexes, arguably the most studied class of anti-cancer drugs targeting nucleic acids. We show that the extension of the original in-cell NMR approach is not straightforward. The severe signal broadening and overlap of H-1 in-cell NMR spectra of polymorphic G-quadruplexes and their complexes complicate their quantitative interpretation. Nevertheless, the H-1 in-cell NMR can be used to identify drugs that, despite strong interaction in vitro, lose their ability to bind G-quadruplexes in the native environment. The in-cell NMR approach is adjusted to a recently developed 3,5-bis(trifluoromethyl)phenyl probe to monitor the intracellular interaction with ligands using F-19-detected in-cell NMR. The probe allows dissecting polymorphic mixture in terms of number and relative populations of individual G-quadruplex species, including ligand-bound and unbound forms in vitro and in cellulo. Despite the probe's discussed limitations, the F-19-detected in-cell NMR appears to be a promising strategy to profile G-quadruplex-ligand interactions in the complex environment of living cells. ER -
KRAFČÍK, Daniel, Eva IŠTVÁNKOVÁ, Šimon DŽATKO, Pavlína VÍŠKOVÁ, S. FOLDYNOVA-TRANTIRKOVA and Lukáš TRANTÍREK. Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy. \textit{International Journal of Molecular Sciences}. Basel: Multidisciplinary Digital Publishing Institute, 2021, vol.~22, No~11, p.~6042-6055. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms22116042.
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